PMID- 27276999 OWN - NLM STAT- MEDLINE DCOM- 20161219 LR - 20181202 IS - 1471-2377 (Electronic) IS - 1471-2377 (Linking) VI - 16 DP - 2016 Jun 9 TI - PRISM II: an open-label study to assess effectiveness of dextromethorphan/quinidine for pseudobulbar affect in patients with dementia, stroke or traumatic brain injury. PG - 89 LID - 10.1186/s12883-016-0609-0 [doi] LID - 89 AB - BACKGROUND: Phase 3 trials supporting dextromethorphan/quinidine (DM/Q) use as a treatment for pseudobulbar affect (PBA) were conducted in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). The PRISM II study provides additional DM/Q experience with PBA secondary to dementia, stroke, or traumatic brain injury (TBI). METHODS: Participants in this open-label, multicenter, 90-day trial received DM/Q 20/10 mg twice daily. The primary outcome was the Center for Neurologic Study-Lability Scale (CNS-LS), assessing change in PBA episode frequency and severity. The CNS-LS final visit score was compared to baseline (primary analysis) and to the response in a previously conducted placebo-controlled trial with DM/Q in patients with ALS or MS. Secondary outcomes included change in PBA episode count and Clinical Global Impression of Change with respect to PBA as rated by a clinician (CGI-C) and by the patient or caregiver (PGI-C). RESULTS: The study enrolled 367 participants with PBA secondary to dementia, stroke, or TBI. Mean (standard deviation [SD]) CNS-LS score improved significantly from 20.4 (4.4) at baseline to 12.8 (5.0) at Day 90/Final Visit (change, -7.7 [6.1]; P < .001, 95 % CI: -8.4, -7.0). This magnitude of improvement was consistent with DM/Q improvement in the earlier phase-3, placebo-controlled trial (mean [95 % CI] change from baseline, -8.2 [-9.4, -7.0]) and numerically exceeds the improvement seen with placebo in that study (-5.7 [-6.8, -4.7]). Reduction in PBA episode count was 72.3 % at Day 90/Final Visit compared with baseline (P < .001). Scores on CGI-C and PGI-C showed that 76.6 and 72.4 % of participants, respectively, were "much" or "very much" improved with respect to PBA. The most frequently occurring adverse events (AEs) were diarrhea (5.4 %), headache (4.1 %), urinary tract infection (2.7 %), and dizziness (2.5 %); 9.8 % had AEs that led to discontinuation. Serious AEs were reported in 6.3 %; however, none were considered treatment related. CONCLUSIONS: DM/Q was shown to be an effective and well-tolerated treatment for PBA secondary to dementia, stroke, or TBI. The magnitude of PBA improvement was similar to that reported in patients with PBA secondary to ALS or MS, and the adverse event profile was consistent with the known safety profile of DM/Q. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01799941, registered on 25 February 2013. FAU - Hammond, Flora M AU - Hammond FM AD - Physical Medicine and Rehabilitation, Indiana University School of Medicine, Rehabilitation Hospital of Indiana, 4141 Shore Drive, Indianapolis, IN, 46254, USA. Flora.hammond@rhin.com. FAU - Alexander, David N AU - Alexander DN AD - University of California, Los Angeles, CA, USA. FAU - Cutler, Andrew J AU - Cutler AJ AD - Florida Clinical Research Center, LLC, Bradenton, FL, USA. FAU - D'Amico, Stephen AU - D'Amico S AD - Cornerstone Medical Group, Franklin, TN, USA. FAU - Doody, Rachelle S AU - Doody RS AD - Baylor College of Medicine, Houston, TX, USA. FAU - Sauve, William AU - Sauve W AD - TMS NeuroHealth Centers, Richmond, VA, USA. FAU - Zorowitz, Richard D AU - Zorowitz RD AD - MedStar National Rehabilitation Network, Washington, DC, USA. FAU - Davis, Charles S AU - Davis CS AD - CSD Biostatistics, Inc., Tucson, AZ, USA. FAU - Shin, Paul AU - Shin P AD - Avanir Pharmaceuticals, Inc., Aliso Viejo, CA, USA. FAU - Ledon, Fred AU - Ledon F AD - Avanir Pharmaceuticals, Inc., Aliso Viejo, CA, USA. FAU - Yonan, Charles AU - Yonan C AD - Avanir Pharmaceuticals, Inc., Aliso Viejo, CA, USA. FAU - Formella, Andrea E AU - Formella AE AD - Avanir Pharmaceuticals, Inc., Aliso Viejo, CA, USA. FAU - Siffert, Joao AU - Siffert J AD - Avanir Pharmaceuticals, Inc., Aliso Viejo, CA, USA. LA - eng SI - ClinicalTrials.gov/NCT01799941 PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20160609 PL - England TA - BMC Neurol JT - BMC neurology JID - 100968555 RN - 0 (Drug Combinations) RN - 0 (Excitatory Amino Acid Antagonists) RN - 0 (dextromethorphan - quinidine combination) RN - 7355X3ROTS (Dextromethorphan) RN - ITX08688JL (Quinidine) SB - IM EIN - BMC Neurol. 2016;16(1):160. PMID: 27590297 MH - Aged MH - Brain Injuries, Traumatic/complications MH - Dementia/complications MH - Dextromethorphan/administration & dosage/*therapeutic use MH - Drug Administration Schedule MH - Drug Combinations MH - Excitatory Amino Acid Antagonists/administration & dosage/*therapeutic use MH - Female MH - Humans MH - Male MH - Middle Aged MH - Pseudobulbar Palsy/complications/*drug therapy MH - Quinidine/administration & dosage/*therapeutic use MH - Severity of Illness Index MH - Stroke/complications MH - Treatment Outcome PMC - PMC4899919 OTO - NOTNLM OT - Brain injuries OT - Center for neurologic study-lability scale OT - Dementia OT - Dextromethorphan OT - Neuropsychiatric symptoms OT - Pseudobulbar affect OT - Quinidine OT - Stroke EDAT- 2016/06/10 06:00 MHDA- 2016/12/20 06:00 PMCR- 2016/06/09 CRDT- 2016/06/10 06:00 PHST- 2015/12/22 00:00 [received] PHST- 2016/05/23 00:00 [accepted] PHST- 2016/06/10 06:00 [entrez] PHST- 2016/06/10 06:00 [pubmed] PHST- 2016/12/20 06:00 [medline] PHST- 2016/06/09 00:00 [pmc-release] AID - 10.1186/s12883-016-0609-0 [pii] AID - 609 [pii] AID - 10.1186/s12883-016-0609-0 [doi] PST - epublish SO - BMC Neurol. 2016 Jun 9;16:89. doi: 10.1186/s12883-016-0609-0.